NIH grant: Perinatal human cerebellum development: high-resolution in-vivo and ex-vivo imaging (1R01HD121977-01)

retained text

NIH grant 1R01HD121977-01: Perinatal human cerebellum development: high-resolution in-vivo and ex-vivo imaging
Institute: {'code': 'HD', 'abbreviation': 'NICHD', 'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development', 'admin_org_id': '12500030', 'admin_funding_url': ''}. PI: Lilla  Zollei. Award: $681793.
Start: 2026-06-23T00:00:00.
PROJECT SUMMARY
The human cerebellum undergoes substantial development during the first postnatal year. Due to advances in
neonatal imaging, perinatal cerebellar injury has been increasingly detected in prematurely born infants up to
19%, and the number is even higher in very low birth weight preterm. The consequences of cerebellar injury are
complex, involving developmental delays in motor, language, cognition, and social behaviors. The impact
appears in the first two years of life and continues into school age and adolescence. Numerous studies have
reported a link between neuroimaging findings in neonatal cerebellar abnormalities and subsequent functional
disorders. However, the results are inconclusive, especially in the cases of secondary cerebellum injury, where
massive cerebellar lesions are absent. How the trajectory of structural development contributes to the functional
domains remains to be elucidated. Notably, the role of connective pathways has been largely neglected in
disorders. There is no consensus on evaluating cerebellar development in clinical practice. This problem is
primarily due to the limitation of in vivo imaging techniques, which hinders the development of interventional
strategies and targeted therapy that may mediate the developmental delay at an early age. To close this gap,
this project proposes to map the neuroarchitecture and connectivity development of the human cerebellum within
the first year of postnatal life by leveraging a cross-scale imaging framework. The framework builds upon the
preliminary work of longstanding in vivo infant neuroimaging tool development and ex vivo magnetic resonance
imaging (MRI) and polarization-sensitive optical coherence tomography (PS-OCT) to reveal the human
cerebellum's microscopic structure and fiber pathways. We aim to build high resolution structural and connectivity
atlases from publicly available infant MRI cohorts as well as ultrahigh-resolution structural and connectivity
atlases using 20 postmortem infant samples to characterize neurodevelopment of the cerebellum. By comparing
structure- and connectivity-dependent growth curves in healthy control and preterm infant with or without
cerebellar injury, we aim to identify biomarkers that can predict their developmental outcomes. Our ultimate goal
is twofold: quantitative morphological characterization of the early stages of human cerebellar development and
the improvement in the functional outcomes in preterm infants by enabling early intervention. Successful
completion of the project will advance our knowledge of the underlying structural components supporting the
functional domains in the human cerebellum. The high-resolution in vivo and ex vivo atlases will offer a valuable
reference for future clinical evaluations in neurodevelopmental disorders involving the cerebellum.

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